This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulmonary hypertension (high blood pressure in the lungs) is a leading killer in patients with sickle cell disease (SCD). Regular blood transfusions improve many aspects of SCD but it is not known whether they help prevent pulmonary hypertension. We will examine this question two ways. First, we will compare the degree of pulmonary hypertension in regularly transfused patients with SCD to those who do not receive transfusions;if the transfused patients have significant less pulmonary hypertension it suggests that transfusions are protective. Secondly, we will examine chronically transfused SCD patients before and 72 hours after having a blood transfusion to see if the transfusion acutely changes the blood pressure in the lungs. In addition to looking at lung blood pressure, we will examine the contraction and relaxation of the heart, heart rate variability (an indirect sign of heart health), blood vessel relaxation, volume of blood pumped by the heart, blood oxygenation, and the integrity of the red blood cells as these variables are all associated with changes in lung blood pressure. Specific Aim 1: Determine the prevalence of pulmonary hypertension and endothelial dysfunction in a group of patients with sickle cell anemia on chronic transfusion therapy. Specific Aim 2: Identify predictors of pulmonary hypertension and endothelial dysfunction in the subgroup of patients with sickle cell anemia on chronic transfusion therapy. Specific Aim 3: Identify acute effects of transfusion therapy on TR jet velocity, hemolysis, hypoxia, cardiac diastolic function, and endothelial function.